Brain tumors are the most common solid tumor diagnosed in childhood and thus account for significant childhood mortality in the United States. Low-grade astrocytomas and gliomas (LGG) are the most common type of brain tumor of childhood (36% of childhood brain tumors). Based on data from the Surveillance, Epidemiology, and End Results (SEER) database published in 2009, it is estimated that the incidence of LGG in the pediatric population is 4,600 cases diagnosed annually in the US. Radiotherapy is avoided or delayed in the treatment of LGG to prevent neurocognitive decline and to prevent transformation to a more malignant grade of tumor (grade III and IV). In this proposal, it is hypothesized that LGG are more likely to respond to poly-ICLC (a TLR3 agonist) and that characterization of signaling pathways for TLR3 in the tumor and stromal compartment will predict response to this therapy. This is an open label, multi-institutional, phase 2 clinical trial of poly-ICLC with dosing of 20 mcg/kg body weight/dose administered intramuscularly (IM) twice weekly to determine the radiographic response rate to poly-ICLC in the treatment of children with recurrent or progressive LGG. Total length of therapy will be two years with each cycle being 28 days in length. The three specific aims are to: 1) determine if poly-ICLC has antitumor activity in the treatment of pediatric recurrent LGG, 2) determine the toxicity of this agent in a LGG cohort and to evaluate a QOL endpoint in patients treated with poly-ICLC, and 3) perform extensive molecular profiling of peripheral blood mononuclear cells (PBMCs), serum and cerebral spinal fluid in patients samples before and after treatment with poly-ICLC in an effort to identify a biomarker signature that will predict responsiveness to this therapy.